Organophosphate pesticides have been identified by the NINDS CounterACT Program as one of the highest priority chemical threats for civilians. Pesticide exposure can cause death, severe seizures, brain injury, cognitive deficits and epilepsy. We have developed the first survival model in the rat for acute paraoxon and DFP induced status epilepticus. We have also identified chronic neurological morbidities in these animals. Our research has shown that pharmacological blockade of the calcium plateau provides neuroprotection following paraoxon intoxication and provides useful strategies to develop treatments to prevent mortality and morbidity associated with organophosphate exposure.
Our new U01 research project in response to PAR-16-331: Optimization of Therapeutic Lead Compounds addresses the major problem of the significant mortality and morbidity following organophosphate- induced status epilepticus. This research effort is focused on using the CounterACT lead compounds atenolol and levetiracetam as effective intramuscular adjunct therapy to reduce both the mortality and the chronic neurological morbidity associated with survival following organophosphate intoxication using currently approved therapies.